Project Summary ? PROJECT 4: JI, Joanne Yew The microbial communities of different individuals exhibit highly diverse and distinctive compositions, a situation that is believed to underlie interpersonal differences in the metabolism of foods and drugs and susceptibility to a range of diseases, including obesity and immune disorders. The long-term objectives of the proposed research are to understand the environmental and genetic factors that change the composition of the microbial community and the ensuing effects on human health and physiology. To study this complex dynamic, a simple model system will be used, with a relatively simple microbiome composition that is amenable to experimental manipulation. The Hawaiian Drosophila (pomace fly) clade consists of nearly 1000 different species that have evolved from a single ancestral species to live on highly diverse plant diets throughout Hawaii. Intriguingly, many of the species exhibit life-long affiliation with a single host plant clade and the distinct microbial communities associated with it. This unique feature provides a powerful opportunity to examine how the microbiome is shaped by the interplay of environmental (e.g., dietary) and genetic factors, and whether dietary perturbation alters host microbiome composition and compromises health. This proposal will test the hypothesis that an organism's microbial diversity is largely governed by environmental rather than genetic factors, and the selective incorporation of microbes from dietary sources confers significant benefits for the organism's development and health. The specific aims of the proposed research are to (i) characterize the composition of microbial communities in natural populations of Hawaiian Drosophila spp. and their host plants; (ii) determine the influence of diet on host microbial composition and the contribution of diet-acquired microbes to host physiology; and (iii) determine the influence of genetic background on host microbial composition. These aims will be achieved using next-generation sequencing to profile microbe communities, manipulation of dietary microbes, and measurements of physiological features such as lipids, lifespan, and fertility.